“Treatment of Neoplasms with Viruses” (WO 00/62735) relates to a method of administering viruses that are able to replicate and kill neoplastic cells with a deficiency in the IFN-mediated antiviral response. One specific aspect of this patent involves the “systemic” administration of such viruses.
Paramyxoviruses are known to interact with erythrocytes and agglutinate them. They are reported to elute from erythrocytes with lower efficiency than influenza viruses. Howe, C. and Lee, L. T. (Adv. Virus Res. 17:1-50, 1972). Furthermore, the specific inhibition of hemagglutination of erythrocytes caused by paramyxoviruses through neutralization by antibodies specific to viral coat proteins is a well understood phenomenon.
Schirrmacher et al (Int. J of Oncology 16:363-373, 2000) have shown that NDV will activate mouse macrophages for anti-tumor activity. The experimental results appearing below demonstrate that NDV does not preferentially bind to mouse leukocytes when added to mouse whole blood.
Bonina et al (Giorn. Batt. Virol. Immun., LXXVIII, 254-261, 1985) show that human macrophages could support the growth of NDV.
Woodruff et al (Cellular Immunology 5:296-306, 1972) and Woodruff and Woodruff (J of Immunology 112 (6);2176-2183, 1974) found that NDV agglutinates rat, mouse and human lymphocytes in vitro.
Faden et al (Blood, 58:221-7,1981) showed that NDV will bind to human neutrophils in vitro.
None of the above indicate any preferential binding of NDV to leukocytes over erythrocytes.
The literature describes the binding of NDV to red blood cells (usually chicken). As NDV is not pathogenic in man it is a surprising result to find that NDV binds preferentially to the white blood cell component of human blood.
The literature indicates that the binding of NDV to cells occurs through the interaction of the Neuraminidase of the viral HN protein with sialic acid residues attached to cell surface proteins. Human erythrocytes have a very high density of sialic acid residues attached to surface proteins. The ratio of erythrocytes to leukocytes in human blood is approximately 1000 to 1. Thus, it is especially surprising that NDV binds to the leukocyte fraction instead of the much more numerous erythrocytes.